Dosing: Adult For oral administrationThe usual daily dose is 500 mg in divided doses for 7 to 10 days, although up to 2 g/day, in three or four divided doses, have been used in severe cases. The total daily dosage should not exceed 2 g.Dosing: PediatricThe usual daily dose is 40 mg/kg in three or four divided doses, for 7 to 10 days. The total daily dosage should not exceed 2 g.

Dosing: Geriatric Refer to adult dosing.

Use

Vancomycin may be used orally for the treatment of staphylococcai enterocolitis and pseudomembranous colitis due to Clostridium difficile.Vancomycin is not significantly absorbed from the normal gastro-intestinal tract and is therefore not effective by the oral route for other types of infection. Intravenous administration may be used concomitantly if required.Consideration should be given to official guidance on the appropriate use of antibacterial agents.

Adverse Reactions

Since vancomycin is not usually significantly absorbed from the gastro-intestinal tract, the toxicity encountered with parenteral therapy is unlikely to occur after oral administration (but see 'Precautions').Nephrotoxicity: Rarely, renal failure, principally manifested by increased serum creatinine or blood urea concentrations, have been observed, especially in patients given large doses of intravenously administered vancomycin. Rare cases of interstitial nephritis have been reported. Most occurred in patients who were given aminoglycosides concomitantly or who had pre-existing kidney dysfunction. When vancomycin was discontinued, azotaemia resolved in most patients.Ototoxicity: Hearing loss associated with intravenously administered vancomycin has been reported. Most of these patients had kidney dysfunction, pre-existing hearing loss, or concomitant treatment with an ototoxic drug. Vertigo, dizziness and tinnitus have been reported rarely.Haematological: Reversible neutropenia, usually starting one week or more after onset of intravenous therapy or after a total dose of more than 25g, Neutropenia appears to be promptly reversible when vancomycin is discontinued. Thrombocytopenia and reversible agranulocytosis (granulocyte count less than 5oo/mm3) have been reported rarely. Eosinophilia has been reported rarely.Miscellaneous: Hypersensitivity reactions, anaphylaxis, chills, drug fever, hypotension, wheezing, dyspnoea, urticaria, pruritus, flushing of the upper body ('red neck syndrome'), pain, muscle spasm of the chest and back, nausea and rashes, including exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis and rare cases of vasculitis.

Contraindications

Hypersensitivity to vancomycin.

Warnings / Precautions Drug

Clinically significant serum concentrations have been reported in some patients who have taken multiple oral doses of vancomycin for active C. difficile-induced pseudomembranous colitis. Therefore, monitoring of serum concentrations may be appropriate in these patients.Some patients with inflammatory disorders of the intestinal mucosa may have significant systemic absorption of vancomycin and, therefore, may be at risk for the development of adverse reactions associated with the parenteral administration of vancomycin. The risk is greater in patients with renal impairment. It should be noted that the total systemic and renal clearances of vancomycin are reduced in the elderly. Ototoxicity has occurred in patients receiving vancomycin. It may be transient or permanent. It has been reported mostly in patients who have been given excessive intravenous doses, have an underlying hearing loss, or are receiving concomitant therapy with an ototoxic agent such as an aminoglycoside. Serial tests of auditory function may be helpful in order to minimise the risk of ototoxicity.When treating patients with underlying renal dysfunction or patients receiving concomitant therapy with an aminoglycoside, serial monitoring of renal function should be performed.Prolonged use of vancomycin may result in the overgrowth of non-susceptible organisms. Careful observation of the patient is essential. If superinfection occurs during therapy, appropriate measures should be taken.

Pregnancy Implications Teratology studies have been performed at 5 times the human dose in rats and 3 times the human dose in rabbits, and have revealed no evidence of harm to the foetus due to vancomycin. In a controlled clinical study, the potential ototoxic and nephrotoxic effects of vancomycin hydrochloride on infants were evaluated when the drug was administered to pregnant women for serious staphylococcal infections complicating intravenous drug abuse. Vancomycin hydrochloride was found in cord blood.No sensorineural hearing loss or nephrotoxicity attributable to vancomycin was noted. One infant, whose mother received vancomycin in the third trimester, experienced conductive hearing loss that was not attributable to vancomycin. Because vancomycin was administered only in the second and third trimesters, it is not known whether it causes foetal harm. Therefore vancomycin should be given to a pregnant woman only if clearly needed.

Lactation

Vancomycin hydrochloride is excreted in human milk. Caution should be exercised when vancomycin is administered to a nursing woman.

Mechanism of Action

Vancomycin is a tricyclic glycopeptide antibiotic derived from Amycolatopsis orientalis. The bacterial action of vancomycin results primarily from inhibition of cell-wall biosynthesis. In addition, vancomycin may alter bacterial cell membrane permeability and RNA synthesis. There is no cross-resistance between vancomycin and other classes of antibiotics.Orally administered vancomycin is active against C. difficile (e.g. toxigenic strains implicated in pseudomembranous enterocolitis). It is also active against staphylococci, including Staphylococcus aureus. Vancomycin is not active in vitro against Gram-negative bacilli, mycobacteria or fungi.

Pharmacodynamics / Kinetics

Vancomycin is poorly absorbed from the gastro-intestinal tract. During multiple dosing of 250 mg every 8 hours for 7 doses, faecal concentrations of vancomycin, in volunteers, exceeded 100mg/kg in the majority of samples.No blood concentrations were detected and urinary recovery did not exceed 0.76%Orally administered vancomycin does not usually enter the systemic circulation even when inflammatory lesions are present. Measurable serum concentrations may occur infrequently in patients with active C. difficile-induced pseudomembranous colitis and, in the presence of renal impairment, the possibility of accumulation exists.